Inclusion Criteria
•Aim 1:

• Clinicians (physicians, Nurse Practitioners, Physician Assistants), nurses, community paramedics, administrators, care coordinators, and other stakeholders likely to be engaged in the CACP program.

Inclusion Criteria
•Aim 2:

• Adults (age ≥ 18 years) who are:
  • Currently admitted to the ED, hospital; or are
  • In a pre-hospital setting but being considered for referral to the ED or hospital at Mayo Clinic Rochester, MN and Barron, WI but do not require hospital-level monitoring or care other than services that could be delivered by CPs in the ambulatory setting if such services were available to them.
• Eligible participants have to reside within an approximately 40-mile radius of Rochester, MN or within the service radius of Barron, WI. 
• Participants who require assistance with activities of daily living, or who are at increased risk for falls, need to have a caregiver available at home. For the purposes of the trial, “residence” and “home” refer to the place where the participant will be physically located after clinic, ED, or hospital discharge, and can include a hotel or another housing arrangement (i.e., not only their permanent residence).

Inclusion Criteria
•Aim 3:

• All community paramedics (up to 18), clinicians who referred participants enrolled in the CACP intervention arm (up to 100), administrators involved with the CACP program (up to 30), and Mayo Clinic Ambulance leaders (up to 20) will be surveyed. 
• All community paramedics (up to 18), purposive sample of participants enrolled in the CACP intervention arm (up to 35), and a purposive sample of clinicians, administrators, administrators, and Ambulance leaders (up to 35) will be interviewed.
• Patient participants will be purposively sampled to ensure diversity of geography, age, sex, race and ethnicity, and clinical diagnosis for CACP program referral. Clinician and administrator participants will be purposively sampled to ensure representation of different ED and hospital service lines and frequency of referrals to the CACP program.

Exclusion Criteria
•Aim 1:​​

•  
• ​​​No exclusion criteria.

Exclusion Criteria
•Aim 2:​​

• Referring clinician believes the patient requires referral to the ED (for patients in the pre-hospital setting) or hospital admission (for patients in the ED or hospital)
• Not meeting criteria outlined in the Community Paramedic Referral Guide
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
• Clinical, behavioral, or cognitive instability, determined by the referring clinician or the CACP service
• Living conditions unsafe for CPs to enter (e.g., patient refuses to secure weapons or animals prior to CP’s arrival)
• Enrolled in the trial during an earlier hospitalization or ED visit.

Exclusion Criteria
•Aim 3:​​

• There will be no exclusion criteria for Aim 3 clinicians or other clinical or administrative stakeholders.
• Patient participants will be excluded if they:
  • Have a communication barrier due to medical illness or cognitive impairment; or
  • Are seriously ill or hospitalized at the time of interview recruitment.

Eligibility last updated 3/16/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years old and residing in the US.
• Clinical diagnosis, based on investigator assessment, of type 2 diabetes for at least one year.
• Using a stable insulin dose for at least 3 months, to include A) basal insulin only, or B) MDI, to include CSII (including use of AID systems other than Tandem Control-IQ).
• Total daily insulin dose ≤ 200 units/day.
• Willing to use only aspart (novolog) or lispro (humalog) insulin with the study pump, with no use of concentrated insulin above U-100, long-acting basal insulin injections, or inhaled insulin.
• For females, not currently known to be pregnant If female of childbearing potential, must agree to use a form of contraception to prevent pregnancy while a participant in the study as documented in the study records. A negative serum or urine pregnancy test will be required for all females of child-bearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued.
• HbA1c ≥ 7.5% and ≤ 12% at screening.
• Has current glucagon product to treat severe hypoglycemia (injectable or nasal) at home (will provide prescription if they do not have one).
• Be willing to exercise for 30 minutes or more at least once per week during the main phase of the study.
• Has the ability to read and understand written English.
• Investigator believes that the participant has capacity such that they can provide informed consent and can successfully and safely operate all study devices and is capable of adhering to the protocol and completing the study.

• Prior use of Tandem t:slim X2 insulin pump with Control-IQ technology.
• Two or more episodes of severe hypoglycemia (needing assistance) in the past 6 months.
• History of inpatient psychiatric treatment in the past 6 months.
• History of drug abuse (defined as any illicit drug use) or history of alcohol abuse prior to screening or unwillingness to agree to abstain from illicit drugs throughout the study.
• History of significant heart disease, lung disease, liver disease, chronic kidney disease, or other systemic disease determined by investigator to interfere with the study, or make required exercise unsafe.
• History of significant vision, hearing, or dexterity problems that will impair use of the closed loop system.
• Use of glucocorticoids, beta blockers, sulfonylureas, meglitinides or other medications specifically listed in section 8.3 of the protocol or determined by investigator to interfere with the study.
• Unstable dose of SGLT-2 inhibitor, GLP-1 receptor agonist, or other adjuvant medication or starting a new glucose lowering agent during the trial.
• Unstable dose of any medication used for weight loss or starting a new medication for weight loss during the trial.　
• Abnormal screening electrocardiogram consistent with increased risk during exercise, such as arrhythmia, ischemia, or prolonged QTc interval (> 450 ms).
• History of hemodialysis.
• History of adrenal insufficiency.
• Uncontrolled hypo- or hyperthyroidism.
• Significant diabetes related complications, based on investigator assessment.
• Immediate family member (spouse, biological or legal guardian, child, sibling, parent) who is an investigative site personnel directly affiliated with this study or who is an employee of Tandem Diabetes Care, Inc.

Eligibility last updated 10/26/21. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 7/19/22. Questions regarding updates should be directed to the study team contact.

Subject Population:

• Heart failure patients and healthy subjects

• Ages 18-90

• Age less than 18

• Age 0 or older 
• Females in the second or third trimester of pregnancy.
• Females planning to deliver her infant at Mayo Clinic Rochester.
• Females able and willing to provide informed consent.

• Females unable or unwilling to provide consent for self or infant.
• Females planning to commercially or publically bank infant cord blood.

• symptoms of gastroesophageal reflux
• presence of Zenker's diverticulum or cricopharyngeal hypertrophy
• undergoing surgery for Zenker's diverticulum or cricopharyngeal hypertrophy with endoscopic laser cricopharyngeal myotomy
• at least 18 years old

• pregnant women
• children
• prisoners
• adults lacking capacity to consent

• Clinical diagnosis of type 1 diabetes.

• Refusal of permission to use medical records for ongoing research.

• Clinical diagnosis of type 1 diabetes.

• Refusal of permission to use medical records for ongoing research.

• No abdominal surgery (except appendectomy and cholecystectomy)
• Stool culture or Polymerase chain reaction (PCR) positive enteritis with Campylobacter

• History of IBS, Irritable Bowel Disease (IBD) (Crohn's disease or ulcerative colitis), microscopic colitis or celiac disease.
• History of gastroenteritis in six months prior to Campylobacter enteritis
• Pregnancy

• All patients who have undergone treatment for articular cartilage, meniscus or ligament injury between 1996-2015

• Arthritis
• Infection

Patients or adult caregivers with severe cognitive disabilities; patients or adult caregivers who otherwise meet study criteria but do not fall within above inclusion criteria.

• Midlife women, ages 45-60 years old.
• Non-smokers.
• Non-obese.
• Have at least one ovary.
• Free from cardiovascular disease.
• Not taking medications influencing cardiovascular function.

• None.

• Women who will give birth at Mayo Clinic by caesarean-section at term following an uncomplicated pregnancy.

• Multiple pregnancy.
• Known presence of clinical infections (e.g., chorioamnionitis), congenital anomalies or maternal pathologies (i.e., diabetes, hypertension, preeclampsia).
• Intrauterine growth retardation or fetal macrosomia.
• Maternal age under 18 or over 50.
• Maternal body mass index (BMI) of less than 18 and more than 40.
• Pregnancy less than 37 weeks of completed gestation.

Eligibility last updated 2/2/22. Questions regarding updates should be directed to the study team contact.

• Any adult over the age of 18.
• Any patient able to walk unassisted with or without a gait aid.

• Individuals under the age of 18.
• Individuals who are immobile (defined as unable to walk with or without a gait aid).

Eligibility last updated 6/5/23. Questions regarding updates should be directed to the study team contact.

• Mayo Clinic patients scheduled for or being seen in the Healthy Longevity Clinic in the Division of General Internal Medicine.
• 18 years of age or older at time of consent
• Have the ability to provide informed consent
• Have the ability to complete all aspects of this trial.

• < 18 years of age. 

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 4/6/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Challenge Study:  

• Males or females 18 to 70 years of age, inclusive.
• Subjects demonstrate willingness to participate in the study and to perform all required procedures as documented by signed informed consent.
• Subjects must have a diagnosis of celiac disease CeD by intestinal biopsy at least 12 months and positive celiac serology at some point in their evaluation, prior to screening as confirmed by medical records or written physician statement.
• Subjects must have reported following a strict GFD for at least the 12 consecutive months and must be willing to maintain their current diet for the duration of study participation while being in gluten challenge.
• Patients who don’t show mucosal healing with a VH:CD ratio < 2 at the baseline endoscopy will enter the GFD non-healed cohort (see below) and will not undergo gluten challenge.   Ninety percent of patients who are asymptomatic, adhere to GFD and are seronegative have achieved histologic healing.

Exclusion Criteria
•Challenge Study:

• Current diagnosis of any severe complication of CeD, such as refractory CeD (RCD) type I or II, enteropathy-associated T-cell lymphoma (EATL), ulcerative jejunitis, or GI perforation.
• Diagnosis of any chronic, active GI disease other than CeD, such as active, untreated peptic ulcer, eosinophilic esophagitis, erosive esophagitis , ulcerative colitis or Crohn’s disease, microscopic colitis, irritable bowel syndrome, small intestinal bacterial overgrowth, tropical sprue, or other GI and non-GI disorder or prior GI surgery that may, in the Investigator’s opinion, interfere with the assessment of symptoms of abdominal pain, diarrhea, or other components of CeD.
• Selective IgA deficiency, defined as having undetectable levels of serum IgA.
• History of severe reaction to gluten exposure that is considered incapacitating or life-threatening.
• Known or suspected exposure to COVID-19 infection in the 4 weeks before the screening.
• History or presence of any clinically significant disease that, in the opinion of the Investigator may confound the subject’s participation and follow-up in the clinical trial or put the subject at unnecessary risk, including but not limited to: uncontrolled hypertension (BP ≥180/110 mm/Hg), unstable angina, Class II congestive heart failure or major fluid overload, coronary angioplasty or myocardial infarction within the past 6 months, clinically significant arrhythmias or electrocardiogram (ECG) abnormalities, severe chronic pulmonary disease, or any renal, hematologic, GI, immunologic, dermatologic, neurologic, or psychiatric disease.
• History of significant substance or alcohol abuse during the 12 months prior to screening as obtained by medical record and/or subject report.
• Females who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding.
• Participation in another investigational drug or device study or treatment with an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Individuals with uncontrolled clotting disorders or on anti-coagulants that they can’t safely hold prior to endoscopy.
• Participation in clinical trial within 30 days prior to consenting, and 12 months for a clinical trial including a biologic agent.
• Participation in clinical trial with tolerogenic agents.

Inclusion Criteria
•De-challenge Study:

• Males or females, 18 to 70 years of age, inclusive.
• Subjects demonstrate willingness to participate in the study and to perform all required procedures as documented by signed informed consent.
• Newly suspected subjects of CeD, either typical symptoms of CeD or referred to celiac clinic due to positive CeD serology undergoing upper endoscopy. Patients with weak positive serology will not be included in order to maximize the likelihood of the patients qualifying for the dechallenge study.    
• Subjects who are currently not on GFD.

Exclusion Criteria
•De-challenge Study:

• Has a history of chronic inflammatory gastrointestinal disease (example, inflammatory bowel disease, extensive colitis, ulcerative jejunitis, drug induced enteropathy) (Microscopic colitis is not an exclusion criteria).
• Has chronic infectious gastrointestinal illness, or acute infectious gastrointestinal illness within the 4-week period prior to screening.
• Known history of lymphoproliferative disease, including monoclonal gammopathy of unknown significance, lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
• Individuals with uncontrolled clotting disorders or on anti-coagulants that they can’t safely hold prior to endoscopy.
• Known or suspected exposure to COVID-19 infection in the 4 weeks before the screening.
• History or presence of any clinically significant disease that, in the opinion of the Investigator may confound the subject’s participation and follow-up in the clinical trial or put the subject at unnecessary risk, including but not limited to: uncontrolled hypertension, unstable angina, Class II congestive heart failure or major fluid overload, coronary angioplasty or myocardial infarction within the past 6 months, clinically significant arrhythmias or ECG abnormalities, severe chronic pulmonary disease, or any renal, hematologic, GI, immunologic, dermatologic, neurologic, or psychiatric disease.
• History of significant substance or alcohol abuse during the 12 months prior to screening as obtained by medical record and/or subject report.
• Participation in another investigational drug or device study or treatment with an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Participation in clinical trial within 30 days prior to consenting, and 12 months for a clinical trial including a biologic agent.
• Participation in clinical trial with tolerogenic agents
• Participants whose initial biopsies do not reveal villous atrophy will not be followed in the de-challenge group but may be recruited into the potential celiac disease cross sectional group so long as they meet the criteria for inclusion into that group.

Inclusion Criteria
•Controls:

• Subjects (both cases and controls) will include males and non-pregnant females, aged 18-70 years.
• Females of reproductive age or capacity (i.e. not having had tubal ligation or sterilization) will have a pregnancy test performed.

Exclusion Criteria
•Controls:

• Subjects on antibiotics, proton pump inhibitors, aspirin, non-steroidal anti-inflammatory drugs, alcohol intake within 48 hours, a bowel preparation within 4 weeks of the studies, and smokers
• Subjects will be asked not to take any probiotics in the week before testing.
• Any known intestinal inflammation such as GERD, eosinophilic esophagitis, and inflammatory bowel disease.
• Prior gastrointestinal surgery (other than appendectomy)
• Ongoing use of antiplatelet agents or anticoagulants.
• Controls should not have a prior history of or family history of CD.
• Subjects unable to provide informed consent
• The presence of any medical or psychological condition could interfere with the safe performance of the upper endoscopy.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/19/23. Questions regarding updates should be directed to the study team contact.

• Subject is willing and able to provide written informed consent.
• Subject is willing and able to provide up to 50 mL of blood via venipuncture and comply with all other study and sample collection procedures.
• Subject is a female aged 18 through 49 years (inclusive).
• Subject is scheduled to undergo either:
  • Laparotomy or laparoscopy for signs and symptoms of suspected endometriosis;
  • Laparotomy, laparoscopy, or other procedures including, but not limited to, tubal ligation, lysis of adhesions, hysterectomy for benign condition, myomectomy, salpingo-oophorectomy, cystectomy, or diagnostic laparoscopy for indications including, but not limited to, infertility or benign gynecological indications. 

Exclusion Criteria:

• Subject has a history of surgically determined diagnosis of endometriosis (either via visual inspection or histopathology).
• Subject is a female in a pre-menarchal or post-menopausal state or has been rendered surgically menopausal (bilateral oophorectomy) for at least 6 months at Screening.
• Subject is pregnant.
• Subject has an active malignancy.
• Subject is known to have tested positive for human immunodeficiency virus or hepatitis A, B, or C.
• Subject has an active pelvic infection or other infections contraindicated for surgery.
• Subject has participated (+/-3 months of study enrollment) in a clinical trial where an investigational drug was or is planned to be administered.
• Subject is undergoing or has previously undergone masculinizing hormone therapy (testosterone treatment).
• Subject has any general health or behavioral condition that, in the opinion of the investigator, should exclude the subject from participation.

Eligibility last updated 9/21/21. Questions regarding updates should be directed to the study team contact.

• Individuals 18+ years of age.
• Capable of consent.
• Diagnosis of a Congenital Heart Disease.

• Individuals < 18 years of age.
• Unable to consent.
• Unable to undergo a cardiac MRI.

Eligibility last updated 12/21/21. Questions regarding updates should be directed to the study team contact.

• Adult patients, ≥ 18 years old.
• Treated at Mayo Clinic from 2011 to 2019 with pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).
• Alive more than 3 years from the procedure.

• Children < 18 years of age.
• Patients who have undergone pancreatoduodenectomy (PD) for other pathology.

Eligibility last updated 4/26/22. Questions regarding updates should be directed to the study team contact.

• Adults, age ≥ 18 years.
• Any concomitant malignancy being treated with any PD-1 inhibitor (pembrolizumab, nivolumab or cemiplimab) as monotherapy and the presence of inflammatory arthritis defined by:
  • provider documented inflammatory arthritis (meet 2010 EULAR/ACR classification criteria of RA) in one or more large or small joints; and at least one or more of the following:
  • elevated inflammatory markers;
  • supportive imaging and/or supportive synovial fluid analysis.

• Active infection.
• Prior history of the rheumatic disease.
• Any B cell depletion therapy.
• PActive use of high (≥ 30 mg daily) of prednisone or steroid equivalent.
• Clinical features suggestive of non-RA autoimmune rheumatic disease (e.g., lupus, Sjogren’s, psoriatic arthritis, etc.) or axial spondyloarthropathy.

Eligibility last updated 9/21/21. Questions regarding updates should be directed to the study team contact.

Mayo Site

• Children born in four southeast MN counties including Olmsted, Dodge, Goodhue, or Wabasha County between Jan 1st, 1997–Dec 31st, 2020 with age of 3-26 years old.
• Research authorization for using medical record for research.
• Children who have received medical care at only Mayo Clinic. 

Sanford Children's Hospital (for Aim 4 only)

• Children who were born between November 1, 2011, and December 31, 2018.

• No research authorization for using medical record for research.
• Residents living in non-Olmsted, Dodge,Goodhue or Wabasha county address in medical record within one year prior to last follow-up date as of data abstraction.
• Insufficient medical record to ascertain asthma status or other variables.
• Children who left the community before the age of 3 years because API requires medical history at least during the first 3 years of life.
• Adopted children (lack of information on a family history of parents which is one of API criteria).
• Conditions making asthma ascertainment difficult (tracheobronchial foreign body at or about the incidence date of asthma, bullous emphysema or pulmonary fibrosis, PiZZ alpha1-antitrypsin, cystic fibrosis, hypogammaglobulinemia (IgG < 2.0 mg/mL), other immunodeficiency disorder (or conditions identified by the International Union of Immunological Societies at index date of AIICs), primary ciliary dyskinesia, bronchiectasis, or COPD if it is present) and other major chest disease (severe kyphoscoliosis or bronchiectasis) which will be identified by ICD code and free text search.
• Immunodeficiency or immunosuppressive therapy:  Patients who had received immunosuppressive or immunoglobulin therapy or transfusion within twelve months prior to index date of AIICs except corticosteroid burst therapy for asthma exacerbation. 
• Children who weigh below 17 kg (the volume of blood taken from the donors is minimized to be less than 3 mL/kg bodyweight for a venipuncture).
• A history of malignancy at index date of AIICs.

• Diagnosis of fibromuscular dysplasia (FMD), segmental arterial mediolysis, and/or spontaneous coronary artery dissection (SCAD)

• Missing records to determine whether or not they have FMD

• Patients who do not accept to participate in research studies.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/27/22. Questions regarding updates should be directed to the study team contact.

• Adult patients, ≥ 18 years of age.
• Patients testing positive for SARS-CoV-2 and requiring hospitalization at the Mayo Clinic Arizona, Rochester, or Florida campuses.

• Patients < 18 years of age.
• Patients with pre-existing end-stage renal disease; i.e., need for renal replacement therapy (RRT) prior to index hospitalization.

1. Parous women with a history of cornary artery disease (CAD)
2. Women without CAD

1. Women without pregnancies

• Adults ≥ 18 years old.
• Undergoing percutaneous nephrolithotomy at Mayo Clinic Rochester.

• Patients who require Intensive Care Unit admission after surgery.
• Patients who have Clavien grade III or greater postoperative complications requiring additional intervention < 30 days after index procedure.

Eligibility last updated 8/26/21. Questions regarding updates should be directed to the study team contact.

• Pregnant patients seen for prenatal care in Rochester and deliver within the Mayo Clinic Health Systems
• Ability to provide informed written consent
• Known paternity for pregnancy
• Singleton pregnancies

• Mothers < 18 years of age
• Multiple fetuses

Eligibility last updated 9/8/22. Questions regarding updates should be directed to the study team contact.

• Male or female patients, aged 18 years and older.
• Scheduled to undergo gastric surgery for obesity.
• Able to provide written informed consent before participating in the study.
• Able to communicate adequately with the investigator and to comply with the requirements for the entire study.

• Individuals < 18 years old.
• Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study.
• Medications. Opiates and high doses of anticholinergic agents (e.g., amitriptyline greater than 50 mg daily).
• Any other condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study.

Eligibility last updated 9/1/21. Questions regarding updates should be directed to the study team contact.